6^th World Congress on Medicinal Chemistry and Drug Design June 07-08, 2017 Milan,. Italy

Biography:

Malkhaz Getia has completed his PhD from Tbilisi State Medical University and Post-doctoral studies from University of Quebec at Chicoutimi, University of Liege and University of Marseille. He is a Scientific Researcher at the TSMU I K Institute of Pharmacochemistry. He has published more than 22 papers in reputed
journals and has been serving as an Editorial Board Member of reputed journal.

Abstract:

Among the biologically active compounds there are various triterpene glycosides (saponins). In recent years some crude extracts from various species of Georgian flora were obtained at the TSMU I Kutateladze Institute of Pharmacochemistry (Tbilisi, Georgia), namely from the leaves of Colchis ivy (Hedera colchica (K. Koch) – extract with antiulcer activity, from the leaves of Fatsia japonica extract with anti-rheumatic activity (Fatsiflogin) and from the leaves of Hedera helix seu H. caucasigena extract with bronchospasmolytic properties (Causuron). Hederacolchiside F (HcF), Fatsiosid D and Hederasaponin C (HsC) were chosen as the biological and chemical markers for the biological active substances. The UV detection is performed at 205 nm. The chromatographic separation was achieved using a reversed phase column C-18. NMR: Structure elucidation of the markers were carried out using 1H NMR (Bruker Avance 400MHz), 13C (Bruker Avance 100 MHz). The proposed HPLC methods are linear in the range studied (r2>0.999) for all the analyses. Precision, sensitivity and linearity are satisfactory in the range studied. Finally, new, simple, sensitive and reproducible HPLC methods have been developed and validated for the simultaneous quantification of HcF, Fatsiosid D and HsC in the crude extract of Colchis ivy, Fatsiflogin and Causuron.

Biography:

Shimon Ben-Shabat has his expertise in Bio-organic and Medicinal Chemistry combining the following areas: Design and synthesis (structure-activity relationship), drug delivery approaches (pro-drugs), targeting and mechanistic studies and bio-analytical studies. His work centers on the relationships between chemistry and biological activity, including evaluation on different disease models

Abstract:

Phospholipase A2 (PLA2) expression/activity is significantly elevated in inflamed intestinal tissue in inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis. PLA2 hydrolyses the sn-2 fatty acyl bond of phospholipids (PL) liberating a fattyacid and a lysophospholipid. By replacing the sn-2 positioned fatty-acid with a drug, PLA2 may be exploited as a prodrug activating enzyme, liberating the free drug from the PL-complex. Therefore, orally delivered PL-based prodrugs will release the free drug at the inflamed sites, effectively targeting the regions of intestinal inflammation. We have utilized a modern computational approach to simulate the PLA2-mediated activation using the candidate drug, and to predict the most appropriate linker length. We have synthesized PL-diclofenac conjugates and shown in-vitro activation of these synthesized conjugates by isolated bee venom PLA2 and conditioned medium from inflamed Caco-2 cell line. We showed that depending on the linker length between the PL and diclofenac, PLA2 could be exploited as the activating enzyme in-vitro, liberating the free diclofenac from the PL complex. We have compared the computational calculations to our experimental data, and obtained excellent correlation between the in-silico predictions and the in-vitro experiments. The proposed research may significantly improve drug therapy in IBD patients, enabling higher efficacy and lower toxicity profiles.

Recent Publications

1. A Dahan, S Ben-Shabat, N Cohen, S Keinan, I Kurnikov, A Aponick, E M Zimmermann (2016) Phospholipid-based prodrugs for drug targeting in inflammatory bowel disease: Computational optimization and in-vitro correlation. Curr. Top. Med. Chem. 16: 2543-8.

2. A Dahan, E Zimmermann, S Ben-Shabat (2014) Modern prodrug design for targeted oral drug delivery. Molecules 19: 16489-16505.

3. Wolk, S Epstein, V Ioffe-Dahan, S Ben-Shabat, A Dahan (2013) New targeting strategies in drug therapy of inflammatory bowel disease: Mechanistic approaches and opportunities, Expert Opin. Drug Deliv. 10: 1275-1286.

4. A Dahan, G L Amidon, E M Zimmermann (2010) Drug targeting strategies for the treatment of inflammatory bowel disease: A mechanistic update. Expert Rev. Clin. Immunol. 6: 543-550.

5. A Dahan, R Duvdevani, E Dvir, A Elmann, A Hoffman (2007) A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the intestine: In-vivo and in-vitro evaluation of an indomethacin-lecithin conjugate. J. Control Release 119: 86-93.

Biography:

Zhongli Gao is currently a Senior Principal Scientist at Sanofi. He received his PhD in Organic Chemistry from the City University of New York in 1993. Upon graduation, he carried out his Post-doctoral Research on the total synthesis of spinosyn-A supervised by Professor Paquette at Ohio State University. He joined Hoechst Pharmaceuticals, one of the predecessor companies of Sanofi in 1995. He has worked on a broad range of disease areas in CNS, respiratory, inflammation, oncology, and rare disease involving GPCRs, proteases, enzymes, kinases, ion channels and transporters. He has led many projects in advancing compounds into clinical and preclinical decisions.

Abstract:

Scaffold hopping is a technique that generates compounds containing a topologically different scaffold from the parent compound, but with similar or improved activity and other properties. This can be done intellectually by medicinal chemists or by computational algorithm. The technique is based on topological pharmacophore models developed from SAR of the current lead. In scaffold hopping, medicinal chemist’s insights into pharmacophore and SAR are crucial in this iterative process. Scaffold hopping can be used to generate new chemical entity; overcome patent or other limitations for the current leads; generate differentiated series of chemical matters. Common approaches include heterocyclic replacements, bonds formation and cleavage, and topology-based hopping. This presentation will describe medicinal chemistry of H3 receptor antagonist and tryptase inhibitor programs via using scaffold hopping strategy to generate multi-genesis of chemical leads. Through optimization of the leads, clinical candidates were identified. The profile of the candidates and in vivo effects in disease animal models will also be briefly discussed.

Biography:

Matteo Micucci has completed his PhD from Bologna University. He is working on Medicinal Chemistry and Nutraceuticals in the Department of Pharmacy and Biotechnology, University of Bologna. He was a Guest Scientist at University of Naples Federico II, in the research group coordinated by Professor Ernesto Fattorusso. He has published 25 papers in reputed journals.

Abstract:

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder, of multifactorial origin. The pathogenetic mechanisms consist of immune dysregulation, altered intestinal microflora, oxidative stress, defects in the gastrointestinal mucosal barrier and increased permeability, altered intestinal motility, whose interplay leads to the onset of a state of chronic mucosal inflammation. The drugs for IBD treatment include corticosteroids, immunosuppressants, and anti-tumor necrosis factor (TNF)-α antibodies, and new therapeutic molecules, that increase the risk of opportunistic infections and malignancies. Furthermore, their efficacy decreases over time and highlights the need to identify new molecular targets for IBD therapy. Scientific research aims at identifying tools able to affect several targets, with minimal side effects. Nutraceutical identifies foods, or food phytochemicals, of animal or vegetal origin, with pharmaceutical properties. Many vegetal extracts determine several effects towards the gastrointestinal tract, which may result in clinical benefits in subjects suffering from IBD. Castanea sativa Mill. bark extract (ENC), containing high amounts of hydrolyzable tannins, inhibits spasmodic contractions, induced by carbachol, histamine, potassium chloride, and barium chloride in guinea pig ileum and by carbachol or serotonin in guinea pig proximal colon. Furthermore, ENC increases gallbladder contraction and relaxes the sphincter of Oddi, suggesting its chronic administration may result not only in a restoration of gastrointestinal contractility, but also in the prevention of gallstone disease. Also Acacia catechu Willd. extract (ACE) was investigated. ACE contains high amounts of catechins, such as (-)-Epicatechin and (+)-Catechin. This extract decreases, in a concentration-dependent manner, colon and ileum spontaneous contractility. In addition, ACE exerts a calcium antagonistic effect, more potent in proximal colon than in ileum. Furthermore, it exhibits antimicrobial effects against Campylobacter jejuni, Escherichia coli, and Salmonella spp., without inhibiting Bifidobacterium and Lactobacillus. These data support the use of ENC and ACE as co-adjuvant in the treatment of IBD.

Biography:

Gaia Cecchia has done a course in Mathematics from the University of Florence. She graduated in Pharmaceutical Sciences in the year 2012 with a thesis in neuropharmacology with the title: “Memantine and topiramate  in association with hypothermia as neuroprotective agents in the neonatal ischemic encephalopathy”.Since 2012, she is working at the ONLUS-No-profit association ‘Nutrition & Prevention’ with Professor Mario Ciampolini.

Abstract:

Background & Objective: We attempted to train two diabetic adults as we suggested in the first abstract. Diabetic people are different from healthy people in this: they don’t develop any hunger sensation after meal suspension.

Methods: Training: recognizing Hinitial Hunger and associate this sensation to low Blood Glucose (76.6 ± 3.7 mg/dL). We tried to implement this training in two obese, diabetic adults.The two subjects consumed meals devoid of fats and carbohydrates (Very Low Energy Diet, VLED) for 6 to 12 months.

Results: At recruitment the two diabetic subjects (out of two) showed a BMI of 39 and 33 and they neither developed a BG decline to 76.6 ± 3.7 mg/dL nor any hunger sensation after 2-days eating suspension. Then Both subjects lost 13%-20% of their initial body weight; they recovered 76.6 ± 3.7 mg/dL of BG and hunger sensations before one – three meals a day, i.e.: they went out of diabetes.

Conclusion: Diabetes develops by inveterate conditioned intake (when previous energy intake has not been fully exhausted before meals), excessive fattening, excessive post-absorption emission of fatty acids from fatty tissues, permanent loss of BG decline to 76.6 ± 3.7 mg/dL and permanent loss of physiological signals of hunger. A healthy, non-diabetic life may be recovered by a painless loss of 20% body weight (No fats, no carbohydrates) and may be maintained by implementing IHMP at reappearance of hunger sensations. This means accurate energy intake planning instead of hunger endurance.

Biography:

Hilal Kilinç has completed her PhD from Ege University and has received scholarship from the scientific and technological research council of Turkey for 4 months to study at Salerno University under the supervision of Professor Sonia Piacente. Her studies focused on isolation, purification and structural elucidation of secondary metabolites.

Abstract:

Silene genus (Caryophyllaceae) is represented by 119 species, wild and cultivated, in Middle and East Anatolia, Azerbaijan, Iran and Iraq. Due to its wide range of biological and pharmacological effects, Silene species are used as herbal medicine. S. gonosperma, S. morcrooftiana W., S. edgeworthii, S. chlorifolia, S. acaulis, S. floscuculi L. and S. vulgaris have been used in the treatment of eye and skin problems, dysentery, inflammation, colic, malaria and stomach pains, urinary infection, respectively. S. vulgaris has been used for its sedative effect and as an anti-toxic agent. Modern biological studies have shown that Silene species exhibit a wide range of biological actions. It has been reported that S. armeria L. showed moderate antifungal activity against all plant pathogens. S. swertiifolia and S. spergulifolia had a high antibacterial activity against gram negative and positive bacteria. S. montbretiana was collected from Malatya, Turkey in 2010. Air-dried and powdered whole plant material was extracted with MeOH. After filtration, the residue was dissolved in water and then partitioned n-BuOH saturated with H2O. The n-BuOH phase was fractioned over RP-VLC to give eight main fractions. Fractions were subjected to open column chromatography by using normal and reverse phase silica gel as adsorbents. This is the first study that describes the isolation and identification of secondary metabolites from S. montbretiana. In this study, two new steroids (SM 4, SM 16) 2β,3β,14α,20S,25- pentahydroxy-cholest 7-en-6-one, 3-O-β-D-glucopyranosyl,25- O-β-D-glucopyranosyl-3β,25- dihydroxycholest-7-en-6-one, along with eight known compounds (six steroids, one flavonoid, and one cerebroside) were isolated from the methanolic extract. Their structures were elucidated by extensive spectroscopic methods including 1D- and 2D-NMR techniques as well as ESIMS and HRMS analyses.

Acknowledgement

This work is supported by TÜBITAK (114Z226) and Ege University Research Foundation (2012-Fen-047).

Recent Publications

1. Davis, P.H., 1967, Flora of Turkey and East Aegean Islands, Edinburgh University Press, Edinburgh.

2. Kayani , S. et al. 2015, J Ethnopharmacol,164:186-202.

3. Özdemir, E. and Alpınar, K., 2015, J Ethnopharmacol, 166:53-65

4. Moerman, D., 1998, Native American Ethnobotany, Timber Press, Oregon.

5. Leto, C. et al. 2013, J Ethnopharmacol, 146:90-112

6. Ballero, J. and Fresu, I., 1993, Fitoterapia, 64: 141-150.

7. Golovko, V.A. and Bushneva, O.A., 2007, B Exp Biol Med, 143:284-286

8. Bajpai, V.K. et al. 2008, Bioresource Technol, 99:8903-8908.

9. Karamian, R. and Ghasemlou, F., 2013, Int J Agric Crop Sci, 5:305-312.

Biography:

Neeraj Tandon was a scientist g and head in Indian council of medical research, India

Abstract:

Over the last few decades alternative medicines, which are essentially plant based, have experienced a remarkable and steady increase all over the world. India with its rich biodiversity and tradition of use of herbal drugs in health care, holds tremendous opportunity for growth in a multibillion global trade, particularly in the herbal area, which has vast potential for developing multiple products for nutrition and prevention and cure of diseases. Knowledge based value addition would mean exporting value added products rather than merely the raw material, besides leading to wider acceptance of Indian plant based drugs.While herbal medicine can potentially contribute to the advancement of healthcare, many major challenges must be overcome prior to the successful integration of herbal remedies into mainstream medicine. It is a time to revisit plants with an objective of developing multicomponent botanical therapies (MCBT) with the full understanding of Systems Biology in order to develop safer and efficacious drugs. Medicinal and aromatic plants (MAPs) act as a well spring of traditional medicines, herbal drugs, nutraceuticals, new chemical entities as drugs and drug intermediates, sweetners, flavour, fragrances, insecticides, natural cosmetics and a number of health care realted products. No doubt, the MAPs have substantially and significantly contributed to the drug armanetarium of the modern Allopathic system of medicine and towards traditional medicines. Bioresource rich nations will be exploring untapped bioresources to meet the demands. India is blessed with rich biodiversity of bioresources and tremendous traditional knowledge base for healthcare products. At present nearly four billion people of the world use plant derived healthcare products. Each plant part used in our traditional systems of medicine (Ayurveda, Unani & Siddha) is a complex mixture of many primary and secondary metabolites. Developing MCBT will provide much safer and efficacious drugs. Plant drugs sound an answer for prioritized diseases such as protozoal diseases (trypanosomiasis, malaria, filaria, leishmania, amoebiasis), viral diseases (Dengue, herpes, Aids, bird flue), metabolic disorders (inflammation, arthritis, diabetes, hypercholestrolaemia), diseases of less known etiology (cancer, muscular dystrophy, Parkinson’s diseases), cardiovascular and central nervous system disorders and self-inflicted diseases (obesity, depression), HIV/AID etc. Standardisation of raw materials has been one of the major impediments in wider acceptance of herbal drugs. In an effort to address this issue monographs on Quality Standards of important medicinal plants used by the industry are being developed by Indian Council of Medical Research on the basis of WHO guidelines for widely used raw materials involving laboratories of reputed institutions across the country to generate requisite data as per prescribed format. The monographs translate practically generated knowledge into direct utility for the Indian Drug Industry engaged in production of plant based drugs and for the Pharmacopoieal Commissions in India & abroad for developing official quality standards on plant based drugs Special emphasis has been laid on chromatographic finger printing of the extracts and assay using phytochemical reference standards as one of the parameters of identity, purity and quality under this programme. The endeavour has yielded very fruitful results evidenced by the publication of 14 volumes of Quality Standards of Indian Medicinal Plants containing 484 plants. The work continues to progress on remaining potential plants required by the industry. Another programme has been initiated on the isolation of Phytochemical Reference Standards(PRS), a key factor in standardization from selected medicinal plants. The procedure of isolation have been optimised and characterized both on the basis of chromatography and spectroscopy for the benefit of these interested in standardizing drugs. Ninety PRS have been isolated and monographs have been prepared and published as three volumes of Phytochemical Reference Standards of Selected Indian Medicinal plants. The samples of these marker compounds are stored as a repository. The work is continuing on other important PRS. Quality standards for the medicinal plants used in India are absolutely necessary for the drugs and formulations produced from them to be of adequate quality, safety and efficacy for their wider acceptance

Biography:

William G Whitford is Strategic Solutions Leader, GE Healthcare in Logan, UT with over 20 years of experience in biotechnology product and process development. He joined the company as an R&D Leader developing products supporting protein biological and vaccine production in mammalian and invertebrate cell lines. Products he has commercialized include defined hybridoma and perfusion cell culture media, fed-batch supplements and aqueous lipid dispersions. He has published over 250 articles, book chapters and patents in the bioproduction arena.

Abstract:

Interest in microvesicles, exosomes and oncosomes is growing. Applications include 1) Vectors of research or therapeutic cargo, 2) Agents of intercellular communication from stems cells to terminally differentiated tissue to the entire microbiome and 3) Support of clinical diagnostics. There are ongoing efforts to standardize clinically applied vesicle assays and therapeutic cargo vehicles. Reference materials, controls, and performance standards need to be defined for quality assurance in such applications. Sponsors often have their choice of  cell platforms, production formats and culture modes for vesicle product and process development. However, commercial success can be dependent upon the discovery of scalable technologies that can produce very large amounts of sufficiently pure and consistent vesicles in a robust, compliant and cost-effective manner in a cGMP environment. In biopharmaceuticals, continuous biomanufacturing promises heightened process flexibility and a  reduction in product microheterogeneity; construction costs and schedule extent; utilities requirement; manufacturing suite area and classification. The value of single-use implemented and continuous biomanufacturing methods will be reviewed

Biography:

Sánchez-Labastida Luis Angel is a third year Medical student at Escuela Superior de Medicina of Instituto Politécnico Nacional. In 2013, he started working in the Department of Molecular Biology, and in 2015, in the Biochemistry department, searching for possible treatments against cancer.

Abstract:

L5178 cells are an experimental lymphocytic leukemia in mice, associated with hyperplasia of the lymphoid tissues and a high number of circulating malignant lymphocytes and lymphoblast, this cellular line was used to evaluate the activity of a maleimide and a maleimide of phenethylamine, as a possible new treatment for leukemia. Previous studies have shown that α, β-unsaturated compounds have important pharmacological properties, as an anti-tumoral activity, this through reducing glutathione levels and increasing oxidative stress, causing cytotoxicity, reduced viability, and death by apoptosis. As the first step, α, β-unsaturated compounds were designed from phenylethylamine, the two best candidates were selected. New green synthesis techniques were designed for both compounds and were synthesized, the chemical structure and purity were confirmed by NMR 1H and 13C, mass spectrometry and IR. The compounds were tested in an in vitro experiment with L5178-Y cell culture (50,000 cells approximately per well), treated with the compounds at  concentrations of 1x10-3 to 1x10-9 M in both cases. Maleimide derivative showed an activity on cells in concentrations of 1x10-6 to 1x10-4 M, evidenced by the MTT assay at 24 and 48 hours, after that, the field was opened at a concentration between 1x10-6 to 10x10-6 M, and an EC50 of 5x10-6 was obtained. For the case of maleimide, an activity was observed at 1x10-3 to 1x10-5 M, and the open field between 1x10-5 to 1x10-4 M showed an EC50 of 3x10-5 M. The experiment results lead us the possibility to evaluate these compounds in an in vivo models such as survival experiments or LD50 in mice.

Biography:

Szu-Han Chen was born in Taipei, Taiwan, in 1985. She received her B.S. in chemistry from Fu Jen Catholic University in 2008 and her M.S. degree in chemistry from National Taiwan Normal University in 2010. She is a Ph.D. student in the Department of Chemistry, National Taiwan University. Her research interests are in total synthesis of drug molecules as well as medicinal and biological chemistry.

Abstract:

Diels–Alder reactions are particularly useful for the total synthesis of pharmacologically active compounds and natural products. Not only does this strategy construct two new C–C σ-bonds in one step, but it also forms a cyclohexene system with good regio- and stereoselectivity http://medicinalchemistry.pharmaceuticalconferences.com/europe/up to four contiguous stereocenters. Using heteroatom-substituted electron-rich dienes, such as Danishefsky’s diene, usually promotes the normal electron-demand Diels–Alder reactions in highly regioselective fashion.

Tamiflu, the phosphate salt of oseltamivir, is a popular anti-influenza drug in clinical use. Diels–Alder reactions using 1,3-butadiene, 1-timethylsilyoxy-1,3-butadiene, furan, N-Boc-pyrrole and 1-Cbz-1,2-dihydropyridine have been successfully applied to react with appropriate dienophiles for construction of the cyclohexene core structure of oseltamivir.

We synthesized a novel diene precursor bearing both 3-pentoxy and ester groups. Dimerization of this diene was overcome by trapping it in situ using activated alkenes as the dienophiles. Inspired by Shibasaki’s work, we successfully synthesized a racemic mixture of  oseltamivir via a sequence of reactions that comprise acyl azide formation and Curtius rearrangement. The synthesis of optically active oseltamivir via asymmetric Diels–Alder reaction is currently under investigation.

Biography:

Wei-Hsin Hsu received her B.S. from Department of Applied Chemisrty, Nartional Chiao Tung University in Taiwan. She is a M.S. student in the Department of Chemisrty, National Taiwan University.

Abstract:

Tuberculosis, a disease caused by bacterial pathogens Mycobacterium tuberculosis, was regarded as under control in the past decades. However, the multi-drug-resistant tuberculosis (MDR-TB) and extensively-drug-resistant tuberculosis (XDR-TB) have emerged to become a serious global health crisis. In 2015, there were an estimated 10.4 million new TB cases worldwide, including nearly a half million cases of MDR-TB. 1 Bedaquiline and delamanid are the effective drugs for treatment of MDR-TB. However, development of new drugs by targeting different TB proteins is still needed for treatment of the MDR-TB and XDR-TB patients.
GlgE is a maltosyltransferase that uses maltose-1-phosphate as the substrate. GlgE involves in a four-step pathway for the production of α-glucan from trehalose, an essential process for mycobacterial survival. Inhibition of GlgE will cause accumulation of maltose-1-phosphate,2 and trigger the self-poisoning of M. tuberculosis. GlgE becomes an appealing drug target according to the toxic effect and synthetic lethal pathway. As no effective GlgE inhibitor has been discovered, we thus designed and synthesized some potential GlgE inhibitors by mimicking the structure maltose-1-phosphate, the GlgE substrate.

Biography:

Nana Gorgaslidze has completed her PhD from Saint-Petersburg State Chemical-Pharmaceutical Academy. She is the Director of TSMU I Kutateladze Institute of Pharmacochemistry and Professor at the Department of Social and Clinical Pharmacy at Tbilisi State Medical University. She has published more than 80 papers in reputed journals.

Abstract:

In presented work the results of preliminary investigation for standardization of fruit bromelain and stem bromelain are given. Comparative characteristic of some physical-chemical properties of the sample of both species is presented. The effect of cysteine and casein concentration on hydrolysis rate, dependence of casein lysis rate on bromelain concentration and reaction duration is shown. Influence of pH on the activity of both (fruit and stem) of bromelain was studied. Optimal pH value was also established. The dependence on pH is similar in both cases. Optimal value of pH is 7.5 for stem bromelain and 8 for fruit one. Determination of proteolytic activity of bromelain fruit and bromelain stem shows that optimal concentration of cysteine is 0.01-0.02 mole/L (in reaction area with a substrate - 0.004-0.008 mol/l). Further increase of concentration causes the considerable reduction of lysis rate. The speed of casein lysis by bromelain fruit and stem in its concentration 0.5%-2% is unchanged. The rate of casein lysis in both cases is proportional to enzyme concentration within 0.05 g/l-0.25 g/l. The rate of casein lysis is time-proportional in the range 5-20 min. The effect of temperature on the activity of both bromelains (fruit and stem) was studied. It was established that optimal temperature is 55-60ºC in both cases. Thus, investigation allows continuing the work in this direction for preparation of corresponding pharmaceutical product.

Biography:

Giovanna Bergamini has completed her PhD in Virology at the University of Bologna. She was a Post-doctoral Researcher at the European Molecular Biology Laboratory in Heidelberg, Germany. At Cellzome in Heidelberg, she leads Drug Discovery Programs in the Immuno-inflammation Therapeutic area. As a Director of Discovery Biology following acquisition of Cellzome from GSK, she oversees numerous activities on the investigation of drug mode of action across the GSK portfolio. She has published more than 20 papers in high impact journals.

Abstract:

CZ415, a potent ATP-competitive mTOR inhibitor with unprecedented selectivity over other kinases will be presented here. It’s in vivo pharmacokinetic profile will be reported, in addition to a comprehensive characterization of its in vitro activities and ADME data. The suitability of this inhibitor for studying in vivo mTOR biology is shown by the inhibition of target-dependent phosphorylation signaling observed in a mechanistic mouse model following oral administration. The compound reported here is the first ATP-competitive mTOR inhibitor described to show efficacy in a semi-therapeutic collagen induced arthritis (CIA) mouse model

Biography:

Jana Sopkova-de Oliveira Santos has completed her PhD from the University Paris XI (Orsay) and University of Charles (Prague). Since 2012, she is a Professor of General Chemistry and Biophysics at the University of Caen Normandy. She has published more than 110 papers in reputed journals

Abstract:

Protein-protein interactions (PPIs) are involved in many cellular processes; consequently, the discovery of small molecules as modulators of PPIs has become a challenge in medicinal chemistry. Structural mimetics of protein secondary structures could maintain or restore biological functions and should possess biological activity. Actually, the most challenging classes of PPIs are those mediated by β-sheet, which are implicated in a number of diseases. Only a few β-strand mimics have been published to date. This study presents an evaluation of oligothienylpyridyl scaffolds in view of their ability for β-strand mimicry. We have observed that a coplanar arrangement in thienylpyridyl systems can be obtained in several different ways. The presence of a nitrogen and sulfur atom in the junction vicinity introduces a coplanar arrangement as well as the presence on the nitrogen atom in the non-orthosubstituted systems. The introduction of an ortho substituent in a system with a nitrogen atom in the junction vicinity perturbs the two rings somewhat, but the system can achieve the coplanar arrangement, because the energy barrier is very low. The same behavior was observed in a non-ortho-substituted biaryl with only a sulfur atom in the junction vicinity. The X-ray structures showed that the compounds have a tendency to adopt a nearly coplanar conformation and the positions of methyl substituents coincide well with those of i, i + 2nd or i, i + 4th β-strand side chains. Therefore, the thienylpyridine scaffold opens the way to produce coplanar compounds mimicking β-strand side-chain distributions.

Biography:

L Amiranashvili has completed her PhD from I Javakhishvili Tbilisi State University. She is a Research Scientist at Tbilisi State Medical University I Kutateladze Institute of Pharmacochemistry, Department of Plant Biopolymers. She has published more than 40 papers in reputed journals and more than 50 presentations at the international conferences. Her fields of professional interests are Bioorganic and Medicinal Chemistry.

Abstract:

Symphytum asperum and S. caucasicum (prickly or rough comfrey) roots and stems have been used externally as a traditional medicinal plant in treating gastrointestinal and respiratory tract diseases in folk medicine. Previous studies showed that these beneficial properties of comfrey are the result of the presence of numerous bioactive compounds. High-molecular fractions from comfrey were isolated. Based on the IR and NMR spectroscopy data, poly[3-(3,4 dihydroxyphenyl)glyceric acid] (PDPGA) was confirmed to be the major component of these fractions. PDPGA–SA and PDPGA–SC exhibit immunomodulatory (anticomplementary), antioxidant and anti-inflammatory activities and wound-healing property. Phytochemical study of roots/stems of Symphytum asperum Lepech., was carried out in order to define other phenolic constituents. The solid-liquid extraction technique was chosen as the first step for isolation the compounds probably containing the fragments of PDPGA followed by the investigation of the composition of the extracts of S. asperum roots/stems using UHPLC-Q-TOF/MS method. Ultrahigh-pressure liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) analysis of extracts of S. asperum roots/ stems was carried out and revealed the presence of low molecular weight compounds such as caffeic, rosmarinic, chlorogenic and salvianolic acids and several oligomeric compounds. The obtained results showed that the comfrey roots/stems can be used as a source for the isolation of low molecular weight biologically active compounds.

Biography:

Laleh Alisaraie is an Assistant Professor with the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada.

Abstract:

Antibiotic drugs have had an extensive use in recent medical history for their ability to fight infectious diseases. Aminoglycoside antibiotics target gram positive and negative bacteria and are beneficial for several varying medical diseases. However, misuse or overuse of these drugs has resulted in creation and over expression of aminoglycoside modifying enzymes (AMEs), which alter the drugs chemical structure, preventing the antibiotic from reaching the host RNA. The primary focus of this research is the mechanism of chemical alteration of the aminoglycoside antibiotic paromomycin-I by the 3',5" phosphotransferase-IIIa AME and the inhibitory effect of a group of antimicrobial peptides on this enzyme. Molecular docking and Molecular Dynamics (MD) simulations were employed to study the binding mode of selected antibiotics and antibacterial peptides against the phosphotransferase-IIIa enzyme. The analyses of both the conformational changes of the antibiotics ternary complexes and the peptide with the best binding affinity to the enzyme in the presence of ATP were performed usin GROMOS 53a6 force field parameters with SPC water model. An antibacterial peptide, chosen among a small library of selected peptides, yielded a greater binding affinity to the antibiotic binding site than the chosen antibiotics. As well, this peptide contained residues that were determined to occupy the similar space as the antibiotic, yielding an inhibition capability. The different and unique confirmations of the AME were also determined when bound with the either the antibiotic or peptide. The results from this research provide a novel insight into the structure of the enzyme and was able to address questions that were not possible to answer based solely on the available data from the enzymes solved crystal structure. There is currently little information regarding these complexes and the potential antibacterial peptide inhibitors. These analyses will help bind the gap between the available data for future pharmaceutical research and the overall goal of antibiotic resistance prevention.